title: A quantitative structure-activity approach for lipophilicity estimation of antitumor complexes of different metals using microemulsion electrokinetic chromatography.
abstract: Microemulsion electrokinetic chromatography (MEEKC) offers a valuable tool for the rapid and highly productive determination of lipophilicity for metal-based anticancer agents. In this investigation, the MEEKC technique was applied for estimation of n-octanol-water partition coefficient (logP(oct)) of a series of antiproliferative complexes of gallium(III) and iron(III) with (4)N-substituted α-N-heterocyclic thiosemicarbazones. Analysis of relationships between the experimental logP(oct) and the retention factors of compounds showed their satisfactory consistency in the case of single metal sets, as well as for both metals. Since none of available calculation programs allows for evaluating the contribution of central metal ion into logP(oct) (i.e. ΔlogP(oct)) of complexes of different metals, this parameter was measured experimentally, by the standard 'shake-flask' method. Extension of the logP(oct) programs by adding ΔlogP(oct) data resulted in good lipophilicity predictions for the complexes of gallium(III) and iron(III) included in one regression set. Comparison of metal-thiosemicarbazonates under examination in terms of logP(oct) vs. antiproliferative activities (i.e. 50% inhibitory concentration in cancer cells) provided evidence that their cytotoxic potency is associated with the ability to cross the lipid bilayer of the cell-membrane via passive diffusion.
authors.affiliation: Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Kosygin Street 19, 119991 Moscow, Russia.
authors.forename: Lidia S
authors.initials: LS
authors.lastname: Foteeva
authors.forename: Denis A
authors.initials: DA
authors.lastname: Trofimov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kuznetsova
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kowol
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Timerbaev
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000295:instrumentation / Q000379:methods*; D015195:Drug Design; D004655:Emulsions; D008055:Lipids / Q000737:chemistry*; D009942:Organometallic Compounds / Q000032:analysis* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D008055:Lipids; D009942:Organometallic Compounds; D012997:Solvents